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Biomedical subjects

J E Fowler

Publications and source records attributed to J E Fowler.

At least 19 recordsLinked to original sources

Impact of site release vaginal pH buffer cream on introital colonization by gram-negative bacilli.

Colonization of the vaginal introitus by gram-negative bacilli is a critical event in the pathogenesis of bacteriuria and is promoted by an abnormal pH elevation. To determine whether a pH reduction might inhibit colonization we conducted a placebo controlled, crossover study of a site release vaginal pH buffer cream. A total of 12 premenopausal women with a history of urinary tract infection participated in the 12-week investigation. The mean introital pH during application of the placebo and buffer was 4.87 and 4.61, respectively (p less than 0.01). However, the percentage of positive introital cultures during application of the placebo and buffer (40.3 and 35.3, respectively) and the mean density of colonization (23,600 and 22,700 bacteria per ml., respectively) were not significantly different. The percentage of positive introital cultures and the mean colonization density were also not different during application of the placebo and buffer when the patients were retrospectively stratified as light and heavy colonizers. These data suggest that alteration of the introital pH within a range of 4.5 to 5.0 does not influence the growth of uropathogens on the vaginal mucosa.

Buffers

Secretory immunity of the prostate gland.

We investigated the immune response of the prostate to bacteriuria and bacterial prostatitis. In men with no histories of urinary tract infection the ratio of IgG:IgA in the expressed prostatic secretions was less than in the serum; most of the IgA was in the secretory form, and immunoglobulin directed against bacterial antigen was almost never detectable. In contrast antibacterial IgG and IgA were usually detectable in the expressed prostatic secretions of men with recent bacteriuria or bacterial prostatitis. The results of quantitative assays for antibacterial immunoglobulin in the expressed prostatic secretions and serum were consistent with local synthesis and secretion of antibacterial IgA. The immune response of the prostate to bacterial infection has the characteristics of secretory immunity.

Bacteriuria

Extracorporeal shock wave lithotripsy for struvite renal calculi: prospective study with extended followup.

To clarify the significance of retained stone particles after extracorporeal shock wave lithotripsy (ESWL) for struvite renal calculi we followed 22 otherwise healthy women for 16 to 52 months (mean 39 months). Each patient had persistent Proteus mirabilis bacteriuria before ESWL and received a standardized regimen of antimicrobial therapy in the perioperative period only. Of the 22 patients 19 (86%) were cured of the persistent bacteriuria. Of these 19 patients 16 had retained stone particles at the beginning of surveillance and 10 had retained particles at last followup. None of the particles produced symptoms or enlarged. However, 1 of the patients who was rendered stone-free had a P. mirabilis reinfection at 20 months and a new stone developed. Of the 22 patients 3 (14%) had continued persistent P. mirabilis bacteriuria after ESWL. Two patients were subsequently cured of the infection with antibiotics alone (1), and with antibiotics and extraction of a new ureteral stone (1). The remaining patient had expansion of retained stone particles after 51 months of surveillance. We conclude that a stone-free kidney is an unrealistic objective of ESWL monotherapy for struvite renal calculi. However, the treatment usually will eradicate the accompanying persistent bacteriuria and sterile stone particles will not enlarge during the first 2 to 4 years after treatment.

Adult

Priapism associated with the sickle cell hemoglobinopathies: prevalence, natural history and sequelae.

To determine the prevalence and characteristics of priapism associated with sickle cell hemoglobinopathic conditions we interviewed and examined 52 men with sickle cell anemia, 10 with sickle C disease, 3 with sickle B(+)-thalassemia and 19 with sickle cell trait. Of the men 20 with sickle cell anemia (38%) and 1 with sickle B(+)-thalassemia (33%) reported past priapism attacks. Average patient age at onset in the sickle cell anemia patients was 19 years (range 8 to 30 years). Four men had had only 1 attack. The average number of attacks per year in the remaining patients ranged from 1 to 52. Of the patients who reported multiple attacks the average duration of a typical episode and the duration of the longest self-limiting episode was 1.6 and 7.0 hours, respectively. Six patients had experienced 1 attack that persisted for longer than 24 hours. There were no significant differences between the clinical and hematological parameters of the sickle cell anemia patients who did and did not experience priapism or of the priapism patients who had and had not experienced episodes lasting greater than 24 hours. Six patients had been hospitalized for priapism and 4 were treated with a shunting procedure. Of the latter patients 2 were impotent but there was no significant alteration in the sexual function of the other study participants.

Adolescent

Suppression of canine antral gastrin secretion by urine.

Distention of the gastric antrum with an alkaline fluid normally results in the secretion of gastrin. Following gastrocystoplasty in humans, however, hypergastrinemia has not been observed. We explored the possibility that a component of urine may suppress antral gastrin activity in the dog. Partial cystectomy and antral transposition to the bladder (ATB) was performed in five animals and antral transposition to the colon (ATC) was performed in five other dogs to serve as a hypergastrinemic controls. At four and eight weeks after surgery the mean serum gastrin levels in the ATC dogs were significantly greater than the mean preoperative levels (p less than 0.05). In contrast, at four and eight weeks after surgery the mean serum gastrin levels in the ATB animals were significantly less than the mean preoperative levels (p less than 0.05). The antral G-cell density as determined by immunohistochemical study at eight weeks after surgery was greater than normal in the ATC dogs but less than normal in the ATB dogs; but the differences did not achieve statistical significance. In another series of experiments using four other dogs a 4% aqueous peptone solution and a 4% peptone solution in concentrated dog urine were instilled into exteriorized antral pouches. The mean serum gastrin levels at 60 and 90 minutes after instillation of the former were significantly increased (p less than 0.05), but there was little or no change after instillation of the latter. Urine, or a component of urine, appears to suppress canine antral gastrin secretion and may explain the absence of hypergastrinemia following gastrocystoplasty in humans.

Animals

Causes, presentation and survival of fifty-seven patients with necrotizing fasciitis of the male genitalia.

This analysis of our experience with 57 men with necrotizing fasciitis of the genitalia was done to identify prognostic variables and to assess the results of a treatment policy of immediate and, if required, repetitive surgical debridements. The mean age of the patients was 55 years. Thirty-eight patients were alcoholics or diabetics, or both. All of the infections were of a genitourinary, anorectal or cutaneous source. Thirty-five per cent of the infections were confined to the genitalia and 65 per cent extended to the abdominal wall or thigh, or both. Forty-seven patients survived. Survival was associated significantly with a younger age, a serum blood urea nitrogen (BUN) level of less than 50 milligrams per deciliter at presentation, the absence of a constellation of abnormalities at presentation consistent with sepsis and a decreased incidence of major complications after initial débridement (p less than 0.05 to 0.01). Survival was not associated with the extent of infection, the duration of symptoms before hospitalization, systemic risk factors, the source of infection, abnormal findings at presentation (excluding a BUN of greater than 50 milligrams per deciliter) and the bacteriologic factors of the infection. Both localized and extensive necrotizing fasciitis of the male genitalia are potentially lethal disorders that require prompt treatment.

Bacterial Infections

Detection of AFP and HCG in metastatic testicular cancer after treatment with chemotherapy or radiation therapy.

We used an indirect immunoperoxidase technique to detect alpha-fetoprotein (AFP) and human chorionic gonadotropin (HCG) in tissue sections of nine metastatic germ cell tumors excised after treatment with chemotherapy or radiation therapy, and correlated the results with the serum levels of AFP and HCG. In all but 1 case yolk sac tumor (YST) was the only histologic type that reacted for AFP (AFP+) and syncytiotrophoblasts (STB) were the only histologic type that reacted for HCG (HCG+). Among 5 cases with normalization of the serum AFP before surgery, 3 were associated with YST-/AFP-, 1 with YST+/AFP+, and 1 with YST+/AFP- metastases; and among 4 cases with normalization of the serum HCG all were associated with STB-/HCG- metastases. Among 3 cases with persistent elevation of the serum AFP, 1 was associated with YST+/AFP+, 1 with YST+/AFP-, and 1 with YST-/AFP- metastases; and of 2 cases with persistent elevation of the serum HCG, 1 was associated with STB-/HCG- and 1 with STB+/HCG+ metastases. These data suggest that marker normalization in the face of persistent tumor results primarily from eradication of YST and STB, but also from treatment-induced inhibition of AFP and HCG synthesis or secretion.

Adult

ESWL monotherapy for large-volume renal calculi: efficacy and morbidity.

We assessed the efficacy and morbidity of extracorporeal shock-wave lithotripsy (ESWL) monotherapy in the treatment of 25 consecutive patients with large-volume renal calculi (surface area greater than or equal to 5.0 cm2). Eighteen of the calculi were infection (struvite) stones and 7 were sterile stones. In 21 cases internal ureteral stents were positioned before ESWL, but no patient underwent pretreatment percutaneous nephrostomy (PCN) or percutaneous nephrostolithotomy (PNL). An average of 2.1 procedures including ESWL, PCN, or ureteral interventions were required to achieve a stone-free renal collecting system and ureter, or residual stone particles less than 4 mm in diameter confined to the renal collecting system. Sixty percent of the patients required no ancillary procedures after ESWL. There were no differences in the mean duration of hospitalization, need for post-treatment ancillary procedures, time to clearance of ureteral fragments, and incidence of residual stone particles among patients with infection and sterile stones. Of 23 patients observed greater than three months (mean 10.9 mos) after ESWL, 43 percent had residual stone particles in the renal collecting system. Expansion of these particles or stone recurrence in the absence of residual particles has not been observed. We conclude that large volume renal calculi may be managed effectively and safely with ESWL monotherapy.

Adult

Massive renal hemorrhage owing to polyarteritis nodosa.

We report a case of massive renal hemorrhage owing to unsuspected polyarteritis nodosa. The bleeding was ultimately controlled by embolization of the renal artery. The findings on renal angiography and enhanced computerized tomography were characteristic of the disorder and they should be familiar to all urologists.

Adult

Epidermal growth factor and prostatic carcinoma: an immunohistochemical study.

Associations between epidermal growth factor (EGF) and carcinoma of the prostate (CAP) have not been systematically investigated. We used indirect immunohistochemical techniques to demonstrate cytoplasmic EGF in paraffin-embedded sections of the following primary prostatic tissues: benign prostatic hyperplasia (BPH) (N = 10), BPH adjacent to CAP (N = 42), clinically localized CAP (N = 45), untreated metastatic CAP (N = 10), and metastatic CAP after varying periods of androgen deprivation (N = 10). In six of the latter 10 cases biopsies of the primary tumor obtained before androgen deprivation therapy were also available for study. Three of the BPH specimens (6%) and 44 of the CAP specimens (68%) stained. Forty per cent of the localized tumors stained but all untreated and treated metastatic tumors stained (p less than 0.01). There were direct but statistically insignificant correlations between the demonstration of EGF and both the Gleason score of localized and untreated metastatic tumors and the pathologic stage of localized tumors. The proportion of malignant cells stained in EGF positive tumors was similar regardless of Gleason score, pathologic stage or the presence or absence of metastases. However, the proportion of cells stained was greater in five of six specimens obtained during hormonal deprivation compared to specimens of the same tumor obtained before treatment. These data suggest that some prostatic cancers interact with EGF and that the interaction may be influenced by the androgenic milieu.

Adenocarcinoma

Interaction of urinary Tamm-Horsfall protein with transitional cells and transitional epithelium.

Uropathogenic E. coli that express mannose sensitive adhesins adhere to agglutinated urinary Tamm-Horsfall protein (THP) and to exfoliated transitional epithelial cells coated with THP. Whether THP interacts with the transitional epithelium in vivo and facilitates adhesin mediated attachment of E. coli is not known. Using immunohistochemical techniques we could not identify THP associated with formalin-fixed, paraffin-embedded transitional epithelium from a variety of sites within the urinary tract. However, varying levels of THP associated with the washed exfoliated transitional cells from 10 different subjects were detected by indirect radioimmunoassay methodologies. After in vitro incubation in human urine the mean interaction of THP with the exfoliated transitional cells increased significantly but closely paralleled the mean interaction of THP with exfoliated vaginal and buccal epithelial cells after identical incubation. We conclude that the interaction of THP with transitional cells in vivo is nonspecific and occurs after detachment from the mucosa. THP may act as a natural host defense against E. coli bacteriuria by inhibition of adhesion mediated bacterial adherence to the urothelium.

Adhesins, Escherichia coli

Small cell undifferentiated carcinoma of the urinary bladder. A light-microscopic, immunocytochemical, and ultrastructural study of 12 cases.

The clinicopathologic, immunocytochemical, and ultrastructural features of 12 small cell undifferentiated carcinomas (SCUCs) of the urinary bladder are herein reported. The patients ranged in age from 50 to 82 years (median, 76 years). Ten patients were male and two were female. Gross hematuria was the most frequent complaint (67%). Five patients died of disease (median survival, 4 months), three patients are still living with unresectable disease after 6, 10, and 12 months, and four patients were only recently diagnosed. Grossly, most of the tumors were large polypoid masses. On light-microscopic examination, they resembled the intermediate and oat cell variants of pulmonary SCUC. Eight SCUC were associated with other forms of in situ or invasive carcinoma, including transitional cell carcinoma (seven cases), adenocarcinoma (three cases), squamous cell carcinoma (three cases), spindle cell carcinoma (one case), and atypical carcinoid tumor (one case). Immunocytochemically, 11 of the 12 tumors expressed one or more epithelial cell markers (epithelial membrane antigen, human milk fat globule protein-2, cytokeratin). Eleven of the 12 SCUCs were also positive for one or more neuroendocrine markers (neuron specific enolase, chromogranin, Leu-7, vasoactive intestinal polypeptide, serotonin). Electron microscopy performed on seven tumors demonstrated dense-core granules (150-250 nm) in all cases, with tonofilaments in four cases, dendrite-like processes in two cases, and intercellular lumina in one case. The clinicopathologic features of 18 previously reported SCUC of the urinary bladder are also reviewed. SCUC arising in this location is an aggressive neoplasm that often demonstrates multidirectional differentiation, including the frequent but not invariable expression of neuroendocrine features.

Aged